Temperature-induced phase transition in methyldopa sesquihydrate revealed via X-ray diffraction, thermal analysis and Raman spectroscopy (original) (raw)
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Pharmaceutical Research, 2012
Purpose To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of atorvastatin. Methods Multivariate curve resolution (MCR) was used to decompose a variable-temperature synchrotron X-ray powder diffraction (VT-XRPD) data matrix into diffraction patterns and concentration profiles of pure drug phases. Results By means of the MCR-estimated diffraction patterns and concentration profiles, the trihydrate phase of the drug salt was found to dehydrate sequentially into two partially dehydrated hydrate structures upon heating from 25 to 110°C, with no associated breakage of the original crystal lattice. During heating from 110 to 140°C, the remaining water was lost from the solid drug salt, which instantly collapsed into a liquid crystalline phase. An isotropic melt was formed above 155°C. Thermogravimetric analysis, hot-stage polarized light microscopy, and hot-stage Raman spectroscopy combined with principal component analysis (PCA) was shown to provide consistent results. Conclusions This study demonstrates that MCR combined with VT-XRPD is a powerful tool for rapid interpretation of complex dehydration behavior of drug hydrates, and it is also the first report on a liquid crystalline phase of the calcium salt of atorvastatin. KEY WORDS calcium atorvastatin. multivariate data analysis. phase transformation. Raman spectroscopy. synchrotron XRPD Electronic supplementary material The online version of this article
International journal of pharmaceutics, 2011
We show in this paper the contribution of the whole Raman spectrum including the phonon spectrum, to detect, identify and characterize polymorphic forms of molecular compounds, and study their stability and transformation. Obtaining these kinds of information is important in the area of pharmaceutical compounds. Two different polymorphic systems are analyzed through investigations in indomethacin and caffeine exposed to variable environmental conditions and various stresses, as possibly throughout the production cycle of the active pharmaceutical ingredient. It is shown the capability of the low-frequency Raman spectroscopy to reveal disorder in the crystalline state, to detect small amorphous or crystalline material, and to elucidate ambiguous polymorphic or polyamorphic situations.
Thermal behaviour and stability in Olanzapine
International journal of …, 2005
The stability and thermal behaviour of two anhydrate phases and a new mixed water:DMSO solvate of Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno-[2,3-b][1,5]benzodiazepine) are studied by different methods: differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Raman scattering (RS). Single crystal structural data for the latter phase are presented, confirming the presence of the (Olanzapine) 2 dimer as the structural building unit of all known phases of the drug, either anhydrate or solvated.
Chemistry and Physics of Lipids, 1997
When a fully hydrated dimyristoylphosphatidylethanolamine (DMPE) is heated from − 50°C with a slow scanning rate ( 0.1°C/min), an exothermic transition peak is observed at around 47 -48°C by differential scanning calorimetry (DSC). This paper deals with the structural change associated with this exothermic transition in a slow heating scan (0.2°C/min). Simultaneous X-ray diffraction and DSC measurements showed that at the exothermic transition, the fully hydrated DMPE cooled to −50°C converts directly from a metastable gel phase to a stable crystalline phase without the appearance of any intermediate phases. This result suggests that a following process occurs: (1) nuclei emerge partly on cooling to −50°C; (2) the nuclei remain unchanged during slow heating until about 43°C; and (3) the nucleation growth becomes active above 43°C.
Journal of Solid State Chemistry, 2003
The crystal structure of dilithium piperazinium(2+) selenate tetrahydrate has been solved; this substance crystallizes in the triclinic space group P % 1; a=7.931(2) (A, b=7.974(2) (A, c=7.991(2) (A, a=106.99(2)1, b=101.83(2)1, g=119.28(2)1 Z=1, R=0.0280 for 1489 observed reflections. A similar compound, dilithium N,N 0-dimethylpiperazinium(2+) selenate tetrahydrate crystallizes in a monoclinic system with space group P2 1 /c and lattice parameters a=7.338(1) (A, b=8.792(2) (A, c=12.856(1) (A, b=92.04(2)1, Z=2, R=0.0334 for 1462 observed reflections. Both structures are centrosymmetric with center of symmetry in the center of eight membered ring formed with two SeO 4 tetrahedra and two LiO 4 tetrahedra connected through tops. The two remaining oxygens on each Li atom come from water molecules. The FTIR and FT Raman spectra of both natural and N,O-deuterated substances have been measured and studied. The thermoanalytical properties were studied using TG, DTG and DTA methods in the temperature range 293-873 K for piperazinium derivative and in the range 293-523 K for dimethylpiperazinium derivative. DSC measurements were carried out in the temperature range 95-343 K. No phase transition was found in this temperature region for either of the compounds.
In situ X-ray diffraction, DSC and Raman spectroscopy thermal investigation of chlorpropamide
Acta Crystallographica Section A Foundations of Crystallography, 2005
In this paper, the main features of Raman spectroscopy, one of the first choice methods in the study of polymorphism in pharmaceuticals, are presented taking chlorpropamide as a case of study. The antidiabetic drug chlorpropamide (1-[4chlorobenzenesulphonyl]-3-propyl urea), which belongs to the sulfonylurea class, is known to exhibit, at least, six polymorphic phases. These forms are characterized not only by variations in their molecular packing but also in their molecular conformation. In this study, the polymorphism of chlorpropamide is discussed on the basis of Raman scattering measurements and quantum mechanical calculations. The main spectroscopic features that fingerprint the crystalline forms are correlated with the corresponding crystalline structures. Using a theoretical approach on the energy dependence of the conformers, simulated molecular torsion angles are plotted versus the formation energy, which provides a satisfactory agreement between the torsion angles at the energy minima and the experimental values observed in the different solid forms of chlorpropamide. Copyright
Physical Chemistry Chemical Physics, 2011
The properties of the intermolecular hydrogen bonds in the monoclinic (Form I) and the orthorhombic (Form II) polymorphs of paracetamol, C 8 H 9 NO 2 , have been studied by single crystal polarized Raman spectroscopy (40 to 3700 cm À1 ) in a wide temperature range (5 K o T o 300 K) in relation to the dynamics of methyl-groups of the two forms. A detailed analysis of the temperature dependence of the wavenumbers, bandwidths and integral intensities of the spectral bands has revealed an essential difference between the two polymorphs in the strength and ordering of OHÁ Á ÁO and NHÁ Á ÁO hydrogen bonds. The compression of intermolecular hydrogen bonds is interrelated with crystal packing and the dynamics of methyl-groups. On structural compression of the orthorhombic polymorph on cooling, a compromise is to be sought between the shortening of OHÁ Á ÁO and NHÁ Á ÁO bonds, attractive CHÁ Á ÁO and repulsive CHÁ Á ÁH contacts in the crystal structure. As a result of a steric conflict at temperatures below 100 K, N-HÁ Á ÁO hydrogen bonds become significantly disordered, and an extended intramolecular transition from the conformation ''staggered'' with respect to the CQO bond to the one ''staggered'' with respect to the NH bond is observed. In most of the studied crystals this transition was only about 60% complete even at 5 K, but in some of the crystals the orientation of all the methyl-groups became staggered with respect to the NH bond at low temperatures. This complete transition was coupled to a sharp shortening of the OHÁ Á ÁO and NHÁ Á ÁO hydrogen bonds at o100 K, the appearance of new additional positions of the protons in these H-bonds, and a slight strengthening of the C-HÁ Á ÁO bonds formed by methyl-groups. The same conformational transition has been observed also in the monoclinic polymorph at T o 80 K. The crystal packing in Form I prevents the O-HÁ Á ÁO hydrogen bonds from adopting the optimum geometry, and they are significantly disordered at all the temperatures, especially at r200 K. The packing of molecules in Form I is also not favourable to form C-HÁ Á ÁO hydrogen bonds involving methyl-groups. One can conclude from the comparison of diffraction and spectroscopic data that the higher stability of Form I results not from a larger strength of individual OHÁ Á ÁO and NHÁ Á ÁO hydrogen bonds, but is a cumulative effect: all the hydrogen bonds together stabilize the structure of the monoclinic polymorph more than that of the orthorhombic polymorph.
International journal of pharmaceutics, 2005
Experiments were conducted to elucidate the relationship between risedronate sodium (RS) hydration state and the physical stability of tablets containing RS. The RS crystal lattice contains channels occupied by water, which is removed by drying processes at temperatures below the boiling point of water, causing a reversible contraction of the crystal lattice. In this study, risedronate sodium was wet granulated followed by fluid bed drying to final granulation moisture contents between 1 and 7%, and then compressed into tablets. During drying, the RS solid-state form was continuously monitored using on-line Raman spectroscopy. Raman spectra acquired in these experiments enabled direct monitoring of changes in the RS crystal lattice, due to dehydration, which provided key information relating RS solid-state form characteristics to final granulation moisture content. Final granulation moisture was found to have a significant effect on the change in RS hydration state measured by Raman...
This article focuses on the development of an innovative method, based on thermodynamic considerations and with the use of Differential Scanning Calorimetry (DSC), for the estimation of the melting enthalpy of crystalline compounds which are metastable near their melting temperature. The curves obtained, at various heating rates, are analysed in two steps. In the first step, the area of a zone generated by the melting endothermic peak is calculated following a specific method. In the second step, the melting enthalpy is extracted from this area through an enthalpy balance. This method is applied to both identified crystallographic forms, named form I and form II, respectively, of Etiracetam (UCB Pharma). The results show that the melting enthalpy of the stable form II compare well with the ones obtained using conventional methods. The curves of the metastable form I present thermal instabilities (partial solid-solid polymorphic transition and beta-recrystallization) near the form I melting peak leading to difficulties for a direct determination of the melting enthalpy by conventional methods. The proposed method is therefore very useful for the estimation of the form I melting enthalpy.
Journal of Raman Spectroscopy, 2006
Polarized Raman scattering studies at room temperature were carried out on N-diethylenediammonium monohydrogenmonophosphate dihydrate single crystal samples, abbreviated N-DDHP. An assignment of the normal modes is proposed based on group theory analysis and correlations with previous data reported for other homologous hydrogen-bonded systems. A careful analysis of the vibrational spectra shows that the assignment of the fundamental vibrational modes can be done based on phosphate, organic and water group vibrations. In addition, differential scanning calorimetry measurement and a Raman spectroscopic study at several temperatures in the range 100-300 K are presented. The occurrence of a lowtemperature phase transition near 220 K is well evidenced. From the temperature-dependence behavior of some internal and external modes, this transition is interpreted by an order-disorder transition which involves the structural modifications of both anion and cation groups.